Abstract This national study addresses the most salient psychosocial causes of the reversal in the decline in midlife mortality for U.S. white non-Hispanics of lower educational attainment since 1998, largely due to death rates from drug and alcohol poisoning and suicide. The specific aims are to 1. Empirically demonstrate the associations between individual chronic stressors and community-level stressors, alcohol and drug abuse, and health outcomes over time among middle-aged whites compared to non-Hispanic blacks linked with educational attainment and 2. Model the salient mediators and moderators of the relationships between chronic stressors, alcohol and drug abuse, and health outcomes in middle-aged individuals, including social- psychological factors (perceived achievement limitations compared to salient reference group), social engagement (social support, political engagement, religious involvement, marital/partner status) and access to and utilization of health, mental health and substance abuse services. Our theoretical model embodies factors derived from reference group theory, social engagement versus anomie and lack of access to health, mental health and substance abuse services to treat stressor-derived symptomatology which may be alternatively self-medicated with alcohol and drugs and negatively impact health. Our hypotheses will be tested by conducting a longitudinal four wave mail survey (N=2500 at wave 1). We will utilize a nationwide address- based sample of middle-aged adults (40-60), oversampling by race, educational attainment and rural versus urban/suburban location. Data analytical techniques will include structural equation modelling and longitudinal growth curve analyses. Qualitative interviews with a small sub- sample of respondents (N=40) will explore how and why the main hypothesized factors predict alcohol and drug abuse and diminished health over time differentially for whites compared to non-Hispanic blacks. The findings from this study will contribute to the formulation of evidence- based social policies and treatment interventions with the most promise for halting increased midlife mortality in an understudied group at high risk for alcohol and drug abuse.